CSHL 2008, Session II: Genome stability, damage & repair

In this first entry on Session II, I’ll focus on the non-telomere-related talks from this session:

Jan Vijg gave a review of his published data about stochasticity and transcriptional noise in response to aging and damage. He also described some newer analysis suggesting that transcriptional noise is present in young animals as well, but that the variation for a given gene depends on the function of that gene — in other words, different functional categories of genes generally exhibited different variation profiles.

Christian Beauséjour argued that mice do not clear DNA-damaged cells — in particular, that neither the adaptive nor the innate immune system is involved in eliminating cells exhibiting signs of persistent DNA damage. This is a foray into controversial territory: Recently published data from other labs suggests that DNA damage causes cells to express ligands for immune cells, resulting in attack and clearance by e.g. NK cells. Beauséjour could reproduce these findings in marrow stem cells (the cell type used in the earlier studies) in vitro, but observed no evidence of clearance of damaged MSCs in vivo.

Philipp Oberdoerffer (from David Sinclair’s lab) asked: What drives chromatin reorganization and how does it relate to mammalian aging? Based on findings in yeast, he looked at mammalian SIRT1 relocalization in response to genotoxic stress, and found that SIRT1 is transiently associated with DNA double-strand break sites.